meningioma
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Meningioma
Author: Georges Haddad, MD, Clinical Assistant Professor, Department of Medicine,Division of Neurosurgery, American University of Beirut, Lebanon
Coauthor(s): Ali Turkmani, MD, Staff Physician, Department of Neurosurgery,American University Hospital; Tarafa Baghdadi, MD, Staff Physician, Department of
Neurosurgery, American University Hospital; Roukoz B Chamoun, MD, Staff Physician, Department of Neurosurgery, American University of Beirut Medical Center
Contributor Information and Disclosures
Updated: Jun 30, 2009
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Overview• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• Multimedia
• References
• Keywords
• Further Reading
Introduction
Background
Meningioma, the term coined by Harvey Cushing, refers to a set of tumors that arisecontiguously to the meninges.
Pathophysiology
Meningiomas may occur intracranially or within the spinal canal. They are thought toarise from arachnoidal cap cells, which reside in the arachnoid layer covering the surface
of the brain.
Meningiomas commonly are found at the surface of the brain, either over the convexity
or at the skull base. In rare cases, meningiomas occur in an intraventricular or intraosseous location. The problem of classifying meningioma is that arachnoidal cells
may express both mesenchymal and epithelial characteristics. Other mesodermal
structures also may give rise to similar tumors (eg, hemangiopericytomas or sarcomas).The classification of all of these tumors together is controversial. The current trend is to
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separate unequivocal meningiomas from other less well-defined neoplasms.
Undoubtedly, advances in molecular biology will allow scientists to determine the exact
genomic aberration responsible for each specific neoplasm.
Frequency
United States
The annual incidence of symptomatic meningiomas is approximately 2 cases per 100,000
individuals. Meningiomas account for approximately 20% of all primary intracranial
neoplasms. However, the true prevalence is likely higher than this because autopsy
studies reveal that 2.3% of individuals have undiagnosed asymptomatic meningiomas.Meningiomas are multiple in 5-40% of cases, particularly when they associated with
neurofibromatosis type 2 (NF2). Familial meningiomas are rare unless associated with
NF2.1
International
The frequency of meningiomas in Africa is nearly 30% of all primary intracranial tumors.
Mortality/Morbidity
Mortality and morbidity rates for meningiomas are difficult to assess. Some meningiomasare discovered fortuitously when CT or MRI is done to assess for unrelated diseases or
conditions. Therefore, some patients die with meningioma and not from it. Estimates of
the 5-year survival usually range from 73-94%.
• Meningiomas usually grow slowly, and they may produce severe morbidity before causing death.
• Factors that may be predictive of a high postoperative morbidity rate include
patient-related factors (eg, advanced age, comorbid states such as diabetes or
coronary artery disease, preoperative neurological status), tumor factors (eg,location, size, consistency, vascularity, vascular or neural involvement), previous
surgery, or previous radiation therapy.
Race
Meningiomas are more prevalent in Africa than in North America or Europe. In Los
Angeles County, meningioma is reported more commonly in African Americans than inothers.
Sex
Meningiomas afflict women more often than men. The male-to-female ratio ranges from1:1.4 to 1:2.8.
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• The female preponderance may be less pronounced in the black population than in
other groups.
• Meningiomas are equally distributed between boys and girls.
Age
The incidence increases with age. Ages and corresponding incidence rates reported from2002 are as follows:
• Age 0-19 years - 0.12
• Age 20-34 years - 0.74
• Age 35-44 years - 2.62
• Age 45-54 years - 4.89
• Age 55-64 years - 7.89
• Age 65-74 years - 12.79
• Age 75-84 years - 17.04
• Age 85 years and older - 18.86
Clinical
History
Meningiomas produce their symptoms by several mechanisms. They may causesymptoms by irritating the underlying cortex, compressing the brain or the cranial nerves,
producing hyperostosis2 and/or invading the overlying soft tissues, or inducing vascular
injuries to the brain. The signs and symptoms secondary to meningiomas may appear or
become exacerbated during pregnancy but usually abate or improve in the postpartum period.
• Irritation: By irritating the underlying cortex, meningiomas can cause seizures.
New-onset seizures in adults justify neuroimaging (eg, MRI) to exclude the
possibility of an intracranial neoplasm.
• Compression: Localized or nonspecific headaches are common. Compression of
the underlying brain can give rise to focal or more generalized cerebral
dysfunction, as evinced by focal weakness, dysphasia, apathy, and/or somnolence.
• Stereotypic symptoms: Meningiomas in specific locations may give rise to the
stereotyped symptoms listed in the Table. These stereotypical symptoms are not
pathognomonic of meningiomas in these locations; they may occur with other
conditions or lesions. Conversely, meningiomas in these locations may remainasymptomatic or produce other unlisted symptoms. Table 1. Symptoms and Signs
Associated with Meningiomas in Specific Locations
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Table
Location Symptoms
Parasagittal Monoparesis of the contralateral leg
Subfrontal Change in mentation, apathy or disinhibited behavior, urinary
incontinenceOlfactory groove Anosmia with possible ipsilateral optic atrophy and
contralateral papilledema (this triad termed Kennedy-Foster syndrome)
Cavernous sinus Multiple cranial nerve deficits (II, III, IV, V, VI), leading to
decreased vision and diplopia with associated facial numbness
Occipital lobe Contralateral hemianopsia
Cerebellopontine
angle
Decreased hearing with possible facial weakness and facial
numbness
Spinal cord Localized spinal pain, Brown-Sequard (hemispinal cord)syndrome
Optic nerve Exophthalmos, monocular loss of vision or blindness,
ipsilateral dilated pupil that does not react to direct light
stimulation but might contract on consensual light stimulation;often, monocular optic nerve swelling with optociliary shunt
vessels
Sphenoid wing Seizures; multiple cranial nerve palsies if the superior orbitalfissure involved
Tentorial May protrude within supratentorial and infratentorial
compartments, producing symptoms by compressing specific
structures within these 2 compartments 3
Foramen magnum Paraparesis, sphincteric troubles, tongue atrophy associatedwith fasciculation
Location Symptoms
Parasagittal Monoparesis of the contralateral leg
Subfrontal Change in mentation, apathy or disinhibited behavior, urinary
incontinence
Olfactory groove Anosmia with possible ipsilateral optic atrophy andcontralateral papilledema (this triad termed Kennedy-Foster
syndrome)
Cavernous sinus Multiple cranial nerve deficits (II, III, IV, V, VI), leading to
decreased vision and diplopia with associated facial numbness
Occipital lobe Contralateral hemianopsiaCerebellopontine
angle
Decreased hearing with possible facial weakness and facial
numbness
Spinal cord Localized spinal pain, Brown-Sequard (hemispinal cord)
syndrome
Optic nerve Exophthalmos, monocular loss of vision or blindness,
ipsilateral dilated pupil that does not react to direct light
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stimulation but might contract on consensual light stimulation;
often, monocular optic nerve swelling with optociliary shuntvessels
Sphenoid wing Seizures; multiple cranial nerve palsies if the superior orbital
fissure involved
Tentorial May protrude within supratentorial and infratentorialcompartments, producing symptoms by compressing specific
structures within these 2 compartments 3
Foramen magnum Paraparesis, sphincteric troubles, tongue atrophy associated
with fasciculation
• Vascular: This presentation, although rare, should be considered. Meningiomas of
the skull base may narrow and even occlude important cerebral arteries, possibly
presenting either as transient ischemic attack (TIA)–like episodes or as stroke.
• Miscellaneous
o Intraventricular meningiomas may present with obstructive
hydrocephalus.
o Meningiomas in the vicinity of the sella turcica may produce panhypopituitarism.
o Meningiomas that compress the visual pathways produce various visual
field defects, depending on their location.
o Rarely, chordoid meningiomas can present with hematologic disturbances,
namely Castleman syndrome.4
Physical
The physical findings mirror the aforementioned symptoms and include signs due to
raised intracranial pressure, involvement of cranial nerves, compression of the underlying
parenchyma, and involvement of bone and subcutaneous tissues by the meningioma.
• Raised intracranial pressure leads to papilledema, decreased mentation and,
ultimately, to brain herniation.
• Involvement of the cranial nerves may lead to anosmia, visual field defects, optic
atrophy, diplopia, decreased facial sensation, facial paresis, decreased hearing,
deviation of the uvula, and hemiatrophy of the tongue.
• Compression of the underlying parenchyma may give rise to pyramidal signs that
are exemplified by pronator drift, hyperreflexia, positive Hoffman sign, and presence of the Babinski sign. Parietal-lobe syndrome may occur if the parietal
lobes are compressed.
o Compression of the dominant (usually left) parietal lobe may give rise to
Gerstmann syndrome: agraphia, acalculia, right-left disorientation, and
finger agnosia.
o Compression of the nondominant (usually right) parietal lobe leads to
tactile and visual extinction and neglect of the contralateral side.o Compression of the occipital lobes leads to a congruent homonymous
hemianopsia.
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• Spinal meningiomas may give rise to a Brown-Sequard syndrome (ie,
contralateral decreased pain sensation, ipsilateral weakness, decrease in position
sense), sphincteric weakness and, ultimately, complete quadriparesis or paraparesis.
Causes
• Trauma and viruses have been investigated as possible causative agents for
development of meningiomas. However, no definitive proof has yet been found.
• The role of inflammation (eg, posttraumatic insult) resulting in the upregulation of
COX-2 has been investigated in the tumorogenesis of meningiomas.5
• On the other hand, the role of radiation in the genesis of meningiomas has been
shown.
o Patients subjected to low-dose irradiation for tinea capitis may develop
multiple meningiomas decades later in the field of irradiation.
o High-dose cranial irradiation may induce meningiomas after a short
latency period.• Genetic causes have been implicated in the development of meningiomas.
o The best-characterized and most common genetic alteration is the loss of
the NF2 gene ( NF2) on chromosome 22q6 . NF2 encodes a tumor
suppressor known as merlin (or schwannomin).
o Of interest, the meningioma locus is close to but probably different from
the gene responsible for NF2.
o Up to 60% of sporadic meningiomas were found to harbor NF2 mutations.
o Other cytogenetic alterations are chromosomal loss of 1p, 3p, 6q, and 14q.
o Loss of chromosome 10 is associated with increased tumor grade,
shortened time to recurrence, and shortened survival.
o Progression to anaplastic meningioma has been associated withinvolvement of chromosomal site 17q.
o The following events were found to be associated with higher grades of
meningiomas: loss of the tumor suppressor in lung cancer-1 gene (TSLC-
1), loss of progesterone receptors, increased expression of cyclooxygenase
2 and ornithine decarboxylase.
o Monosomy of chromosome 7 is a rare cytogenetic change. However, it is
frequently reported in radiation-induced meningiomas.
o The invasive potential of meningioma cells seems to be reflected by a
balance between the expression of matrix metalloproteinases (MMPs) and
tissue inhibitors of MMPs (TIMPs).
o The most consistent chromosomal abnormality isolated in meningiomas ison the long arm of chromosome 22.
o Meningiomas can also be associated with different genetic syndromes,
namely Gorlin7 and Rubinstein-Taybi syndromes8 .
• Several findings suggest an association between hormones and the risk for
meningiomas, including increased incidence in women versus men and the
presence of estrogen, progesterone, and androgen receptors on some of these
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tumors. However, the exact nature of this relationship and its implication on the
management of meningiomas remain under investigation.
• Whether cell phone use increases the risk of meningiomas (and of brain tumors in
general) remains of great interest, especially with the recent tremendous increase
in the use of these devices worldwide. At present, the available data do not
support such an association; however, all published studies have relatively smallsample sizes and a short period of follow-up.9
eMedicine Specialties > Neurology > Neuro-oncology
Meningioma: Differential Diagnoses &
Workup
Author: Georges Haddad, MD, Clinical Assistant Professor, Department of Medicine,
Division of Neurosurgery, American University of Beirut, LebanonCoauthor(s): Ali Turkmani, MD, Staff Physician, Department of Neurosurgery,
American University Hospital; Tarafa Baghdadi, MD, Staff Physician, Department of
Neurosurgery, American University Hospital; Roukoz B Chamoun, MD, Staff Physician, Department of Neurosurgery, American University of Beirut Medical Center
Contributor Information and Disclosures
Updated: Jun 30, 2009
• Print This
• Email This• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• Multimedia
• References
• Keywords
• Further Reading
Differential Diagnoses
Brainstem Gliomas Neurofibromatosis, Type 1
Cavernous Sinus Syndromes Neurofibromatosis, Type 2
Complex Partial Seizures Oligodendroglioma
Craniopharyngioma Persistent Idiopathic Facial PainFrontal Lobe Syndromes Pituitary Tumors
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Glioblastoma Multiforme Primary CNS Lymphoma
Low-Grade Astrocytoma
Other Problems to Be Considered
Back pain
Workup
Laboratory Studies
No specific laboratory tests are used to screen for meningioma.
Imaging Studies
•
Imaging studies are the mainstay of diagnosis (see Media files 1-7).
Case 1: Surgical view of the tumor. The dura is opened, and the meningioma
can be seen extending en plaque over the surface of the brain.
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Case 1: Surgical view of the tumor. The dura is opened, and the meningioma
can be seen extending en plaque over the surface of the brain.
• Plain skull radiograph may reveal hyperostosis and increased vascular markings
of the skull, as well as intracranial calcifications.
• On plain head CT scans, meningiomas are usually dural-based tumors that are
isoattenuating to slightly hyperattenuating.
o They enhance homogeneously and intensely after the injection of
iodinated contrast material.
o Perilesional edema may be extensive. Hyperostosis and intratumoral
calcifications may be present.
o The tumor compresses the brain without invading it.
o Multiple meningiomas may be difficult to differentiate from metastasis.
• On T1- and T2-weighted MRIs, the tumors have variable signal intensity. If a
meningioma is suspected, obtaining an enhanced MRI is imperative.
o
Meningiomas enhance intensely and homogeneously after injection of gadolinium gadopentetate.
o The edema may be more apparent on MRI than on CT scanning.
o An enhancing tail involving the dura may be apparent on MRI.
o Cystic meningiomas may exhibit intratumoral or peritumoral cysts. The
peritumoral cysts may actually represent a gliotic response and may not
necessitate surgical extirpation.
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• Endovascular angiography allows the surgeon to preoperatively determine the
vascularization of the tumor and its encroachment on vital vascular structures.
o Late venous images are important to determine the patency of the involved
dural sinuses.
o Angiographic features of meningiomas include the following:
Supply from the external circulation Mother-in-law blush (which comes early and leaves late)
Sunburst or radial appearance of the feeding arteries
o Although magnetic resonance arteriography (MRA) and magnetic
resonance venography (MRV) have decreased the role of classical
angiography, the latter remains a powerful tool for planning surgery.
o Angiography is still indispensable if embolization of the tumor is deemed
necessary.
• New research tools such as positron emission tomography (PET), including
octreotide-PET, or magnetic resonance spectroscopy (MRS) have been used to
predict in vivo the aggressiveness of meningiomas.10
Procedures
• Preoperative endovascular embolization of the vascular feeders from the external
circulation may be beneficial in extremely vascular meningiomas.11
• If this is the case, resection should be performed shortly after embolization to
decrease the likelihood of tumor revascularization.
Histologic Findings
Meningiomas are usually globular, well-demarcated neoplasms. They have a wide dural
attachment and become invaginated into the underlying brain without invading it. Their cut surface is either translucent pale or homogeneously reddish brown. It may be gritty on
cutting. Some meningiomas occur as a sheetlike extension that covers the dura but does
not invaginate the parenchyma; this variant is called meningioma en plaque. The last
morphologic variant is the cavernous sinus meningioma that infiltrates the cavernoussinus and becomes interdigitated with its contents. The 3 most common histologic
subtypes of meningiomas are the meningothelial (syncytial), transitional, and fibroblastic
meningiomas. See Media files 8-9 for representative pathologic views of varioussubtypes.
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Case 2: Bone flap was removed. Note tumoral breach of the dura. The dura and
overlying skull were removed surgically. Duraplasty and cranioplasty were
performed
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Case 2: Bone flap was removed. Note tumoral breach of the dura. The dura andoverlying skull were removed surgically. Duraplasty and cranioplasty were
performed
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Case 2: Surgical specimen. Complete resection was achieved.
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Case 2: Surgical specimen. Complete resection was achieved.
Meningothelial meningiomas reveal densely packed cells that are arranged in sheets with
no clearly discernible cytoplasmic borders. Although not prominent, whorls are present(calcified whorls are termed psammoma bodies). Nuclei show intranuclear vacuoles.
Fibroblastic (fibrous) meningiomas reveal sheets of interlacing spindle cells. Theintercellular stroma is composed of reticulin and collagen. The transitional variety reveals
features common to both the meningothelial and fibroblastic varieties; others include
angiomatous, microcystic, secretory, clear cell, choroid, lymphoplasmacyte-rich, papillary, and metaplastic variants.
Meningiomas may be associated with hyperostosis.2 The exact nature of the cause of this
hyperostosis is controversial (ie, reactive versus tumoral infiltration).
Immunohistochemistry
Immunohistochemistry can help diagnose meningiomas, which are positive for epithelialmembrane antigen (EMA) in 80% of cases. They stain negative for anti-Leu 7 antibodies
(positive in schwannomas) and for glial fibrillary acidic protein (GFAP). Progesterone
receptors can be demonstrated in the cytosol of meningiomas; the presence of other sex
hormone receptors is much less consistent. Somatostatin receptors also have beendemonstrated consistently in meningiomas.
Malignancy
The notion of malignancy in meningiomas is still vague.12 Some histologic variants, such
as papillary meningioma, undoubtedly carry a less favorable prognosis than other histologic types. Two features are considered clear signs of malignancy: cortical invasion
by the tumor and distal metastasis. Of note, in the 2007 WHO grading scheme, brain
invasion is considered a criterion for atypia.
Several stains have been used to help predict the behavior of meningiomas. These stainsquantify the mitotic rate of these tumors. Bromodeoxyuridine (BudR) labeling requires an
intravenous (IV) injection before tumor removal. On the other hand, immunohistologic
staining for proliferating cell nuclear antigen (PCNA) can be performed on fixed
specimens. Some have attempted to correlate the pathology and behavior of meningiomasto the loss of specific genetic material.
The World Health Organization classification of meningiomas is presented in Table 2.
Table 2. Summary of the 2007 WHO Grading Scheme for Meningiomas
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Table
WHO
Grade Histological Subtype Histological Features I Meningothelial, fibroblastic,
transitional, angiomatous,
microcystic, secretory,lymphoplasmacytic metaplastic,
psammomatous
Does not fulfill criteria for grade II or III
II (Atypical) Chordoid, clear cell 4 or more mitotic cells per 10 hpf and/or
3 or more of the following: increasedcellularity, small cells, necrosis,
prominent nucleoli, sheeting, and/or
brain invasion in an otherwise Grade I
tumor III
(Anaplastic)
Papillary, rhabdoid 13 20 or more mitoses per 10 hpf and/or
obviously malignant cytologicalcharacteristics such that tumor cell
resembles carcinoma, sarcoma, or
melanoma
WHO
Grade Histological Subtype Histological Features
I Meningothelial, fibroblastic,
transitional, angiomatous,microcystic, secretory,
lymphoplasmacytic metaplastic, psammomatous
Does not fulfill criteria for grade II or III
II (Atypical) Chordoid, clear cell 4 or more mitotic cells per 10 hpf and/or 3 or more of the following: increased
cellularity, small cells, necrosis,
prominent nucleoli, sheeting, and/or brain invasion in an otherwise Grade I
tumor
III
(Anaplastic)
Papillary, rhabdoid 13 20 or more mitoses per 10 hpf and/or
obviously malignant cytologicalcharacteristics such that tumor cell
resembles carcinoma, sarcoma, or melanoma